Marcel Cerqueira Cesar Machado

Early survival and safety of ALPPS: first report of the International ALPPS Registry.

Objectives:To assess safety and outcomes of the novel 2-stage hepatectomy, Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS), using an international registry. Background:ALPPS induces accelerated growth of small future liver remnants (FLR) to allow curative resection of liver tumors. There is concern about safety based on reports of higher morbidity and mortality. Methods:A Web-based data entry system was created with password access and data pseudoencryption (NCT01924741). All patients with complete 90-day data were included. Multivariate logistic regression analysis was performed to identify independent risk factors for severe complications and mortality and volume growth of the FLR. Results:Complete data were available for 202 patients. A total of 141 (70%) patients had colorectal liver metastases (CRLM). Median starting standardized future liver remnants of 21% increased by 80% within a median of 7 days. Ninety-day mortality was 19/202 (9%). Severe complications including mortalities (Clavien-Dindo ≥IIIb) occurred in 27% of patients. Independent factors for severe complications were red blood cell transfusion [odds ratio (OR), 5.2), ALPPS stage I operating time greater than 300 minutes (OR, 4.4), age more than 60 years (OR, 3.8), and non-CRLM (OR, 2.7). Age, use of Pringle maneuver, and histologic changes led to less volume growth. In patients younger than 60 years with CRLM, 90-day mortality was similar to conventional 2-stage hepatectomies for CRLM. Conclusions:This is the first analysis of the ALPPS registry showing that ALPPS has increased perioperative morbidity and mortality in older patients but better outcomes in patients with CRLM.

Hepatic Adenoma and Focal Nodular Hyperplasia: Differential Diagnosis and Treatment

The diagnosis of benign hepatic tumors as hepatic adenoma (HA) and focal nodular hyperplasia (FNH) remains a challenge for clinicians and surgeons. The importance of differentiating between these lesions is based on the fact that HA must be surgically resected and FNH can be only observed. A series of 23 female patients with benign liver tumors (13 FNH, 10 HA) were evaluated, and a radiologic diagnostic algorithm was employed with the aim of establishing preoperative criteria for the differential diagnosis. All patients were submitted to surgical biopsy or hepatic resection to confirm the diagnosis. Based only on clinical and laboratory data, distinction was not possible. According to the investigative algorithm, the diagnosis was correct in 82.6% of the cases; but even with the development of imaging methods, which were used in combination, the differentiation was not possible in four patients. For FNH cases scintigraphy presented a sensitivity of 38.4% and specificity of 100%, whereas for HA the sensitivity reached 60% and specificity 85.7%. Magnetic resonance imaging, employed when scintigraphic findings were not typical, presented sensitivities of 71.4% and 80% and specificities of 100% and 100% for FNH and HA, respectively. Preoperative diagnosis of FNH was possible in 10 of 13 (76.9%) patients and was confirmed by histology in all of them. In one case, FNH was misdiagnosed as HA. The diagnosis of HA was possible in 9 of 10 (90%) adenoma cases. Surgical biopsy remains the best method for the differential diagnosis between HA and FNH and must be performed in all doubtful cases. Surgical resection is the treatment of choice for all patients with adenoma and can be performed safely. With the evolution of imaging methods it seems that the preoperative diagnosis of FNH may be considered reliable, thereby avoiding unnecessary surgical resection.

Antimicrobial peptides: clinical relevance and therapeutic implications.

Antimicrobial peptides (AMPs) are molecules that provide protection against environmental pathogens, acting against a large number of microorganisms, including bacteria, fungi, yeast, virus and others. Two major groups of antimicrobial peptides are found in humans: cathelicidins and defensins. Recently, several studies have furnished information that besides their role in infection diseases, antimicrobial peptides play a role in diseases as diverse as inflammatory disorders, autoimmunity and cancer. Here, we discuss the role of antimicrobial peptides and vitamin D have in such complex diseases and propose their use should be more explored in the diagnosis and treatment of such conditions.

Intrahepatic Glissonian approach for laparoscopic right segmental liver resections.

BACKGROUND Experience with laparoscopic procedures and recent advances in laparoscopic devices have created an evolving interest in the application of these techniques to liver resection. However, laparoscopic liver resection has not been widely developed and anatomical segmental liver resection is not currently performed due to difficulty to control segmental Glissonean pedicles laparoscopically. METHODS Seven consecutive patients underwent laparoscopic liver resection using an intrahepatic Glissonian approach from April 2007 to September 2007. Three patients underwent laparoscopic bisegmentectomy 6-7 and 4 patients underwent laparoscopic right hemihepatectomy. RESULTS Blood transfusion was required in 1 patient. Mean operation time was 460 minutes (range 300-630 minutes). The median hospital stay was 5 days (range 3-8 days). One patient developed bile leakage that was treated conservatively. No patient had postoperative signs of liver failure. No postoperative mortality was observed. CONCLUSIONS The main advantage over other techniques is the possibility to gain a rapid and precise access to the right posterior and anterior sheaths facilitating right hemihepatectomy, and right anterior and posterior sectionectomies. We believe that the described technique facilitates laparoscopic liver resection by reducing the technical difficulties in pedicle control and may increase the development of segment-based laparoscopic liver resections.

Management of Hepatic Hemangiomas: A 14-Year Experience

Hemangioma is the most common primary tumor of the liver and its diagnosis has become increasingly prevalent. Most of these lesions are asymptomatic and are managed conservatively. Large hemangiomas are often symptomatic and reports of surgical intervention are becoming increasingly frequent. We present our experience, over the last 14 years, with diagnosis and management of 249 liver hemangiomas, with special attention to a conservative strategy. Clinical presentation, diagnosis, treatment, and longterm outcome are analyzed. Of 249 patients, 77 (30.9%) were symptomatic, usually with right abdominal upper quadrant pain. Diagnosis was based on a radiologic algorithm according to the size and characteristics of the tumor; diagnosis by this method was not possible in only one case (0.4 %). Giant hemangiomas (>4 cm) were found in 68 patients (27.3%) and in 16 were larger than 10 cm. Eight patients (3.2%) underwent surgical treatment; indications were incapacitating pain in 6, diagnostic doubt in 1, and stomach compression in 1. No postoperative complications or mortality were observed in this series. Patients who did not undergo surgery (n = 241) did not present any complication related to the hemangioma during long-term follow-up (mean = 78 months). Hemangioma is a benign course disease with easy diagnosis and management. We propose a conservative approach for these lesions. Resection, which can be safely performed, should be reserved for the rare situations such as untreatable pain, diagnostic uncertainty, or compression of adjacent organs.

Pretreatment CA 19-9 level as a prognostic factor in patients with advanced pancreatic cancer treated with gemcitabine

SummaryBackground. Serum levels of CA 19-9 correlate with survival among patients with pancreatic cancer treated with surgery or radiation therapy. In addition, CA 19-9 responses have been shown to predict for a better prognosis among patients with advanced disease treated with chemotherapy. The present study evaluates the predictive role of CA 19-9 pretreatment levels and response among patients treated with gemcitabine.Methods. We retrospectively identified 28 patients with advanced pancreatic cancer and baseline elevations of CA 19-9 (>37 U/mL) who were treated with single agent gemcitabine. CA 19-9 response was defined as a ≥50% decline at any time after treatment. Survival was estimated with the Kaplan-Meier method, and curves were compared with the log-rank test.Results. Eleven patients (39%) had a CA 19-9 response. The median survival of responding patients was longer than that of non-responding patients (13.8 vs 8 mo, p=.0272). When pretreatment CA 19-9 levels were analyzed, patients who had CA 19-9 below the median for the entire sample (1212 U/mL) lived significantly longer than patients with a CA 19-9 above the median (14.9 vs 7.4 mo, p=.0013). On multivariable analysis, pretreatment CA 19-9 level was an independent, and stronger predictor of survival (p=.0005) than CA 19-9 response (p=.0497). Other variables were not associated with survival.Conclusions. CA 19-9 may be a useful adjunct to response evaluation is this setting. In addition to CA 19-9 responses, prechemotherapy levels of this marker seem to have strong prognostic significance.

Liver mitochondrial dysfunction and oxidative stress in the pathogenesis of experimental nonalcoholic fatty liver disease

Oxidative stress and hepatic mitochondria play a role in the pathogenesis of nonalcoholic fatty liver disease. The aim of the present study was to evaluate the role of hepatic mitochondrial dysfunction and oxidative stress in the pathogenesis of the disease. Fatty liver was induced in Wistar rats with a choline-deficient diet (CD; N = 7) or a high-fat diet enriched with PUFAs-omega-3 (H; N = 7) for 4 weeks. The control group (N = 7) was fed a standard diet. Liver mitochondrial oxidation and phosphorylation were measured polarographically and oxidative stress was estimated on the basis of malondialdehyde and glutathione concentrations. Moderate macrovacuolar liver steatosis was observed in the CD group and mild liver steatosis was observed in the periportal area in the H group. There was an increase in the oxygen consumption rate by liver mitochondria in respiratory state 4 (S4) and a decrease in respiratory control rate (RCR) in the CD group (S4: 32.70 +/- 3.35; RCR: 2.55 +/- 0.15 ng atoms of O2 min-1 mg protein-1) when compared to the H and control groups (S4: 23.09 +/- 1.53, 17.04 +/- 2.03, RCR: 3.15 +/- 0.15, 3.68 +/- 0.15 ng atoms of O2 min-1 mg protein-1, respectively), P < 0.05. Hepatic lipoperoxide concentrations were significantly increased and the concentration of reduced glutathione was significantly reduced in the CD group. A choline-deficient diet causes moderate steatosis with disruption of liver mitochondrial function and increased oxidative stress. These data suggest that lipid peroxidation products can impair the flow of electrons along the respiratory chain, causing overreduction of respiratory chain components and enhanced mitochondrial reactive oxygen species. These findings are important in the pathogenesis of nonalcoholic fatty liver disease.

The impact of clinical and genetic screenings on the management of the multiple endocrine neoplasia type 1

PURPOSE To perform clinical and genetic screening for multiple endocrine neoplasia type 1 (MEN1) in patients at the Academic Hospital of the University of São Paulo School of Medicine, and to analyze its impact on clinical management of patients with MEN1. METHODS The clinical diagnosis of MEN1 was made in accordance with the Consensus on multiple endocrine neoplasias. Mutation analysis of the entire MEN1 tumor suppressor gene and genetic screening of at-risk family members were performed by direct sequencing. To analyze the implementation of genetic diagnosis, the studied patients were separated into 3 groups: MEN1 index cases (group I), clinically diagnosed MEN1 cases (group II), and genetically diagnosed MEN1 cases (group III). RESULTS In total, 154 individuals were clinically and genetically studied. We identified 12 different MEN1 mutations. Fifty-two MEN1 cases were identified: 13 in group I, 28 in group II, and 11 in group III. The mean age in group III (27.0 years) was significantly lower than in groups I (39.5 years) and II (42.4 years; P = 0.03 and P = 0.01, respectively). Patients in groups I and II mostly presented 2 or 3 MEN1-related tumors, while 81.8% of those in group III presented 1 or no MEN1-related tumor. Additionally, in group III, 45.4% of cases were asymptomatic, and no metastasis or death was verified. Surveillance for MEN1 mutations allowed the exclusion of 102 noncarriers, including a case of MEN1 phenocopy. CONCLUSION Our data supports the benefits of clinical and genetic screening for multiple endocrine neoplasia type 1 in the management of this syndrome.

MRI features of groove pancreatitis

OBJECTIVE The purpose of this article is to discuss and illustrate the most relevant and unique MRI features of groove pancreatitis. CONCLUSION Groove pancreatitis in an uncommon type of focal chronic pancreatitis. Its appearance may resemble pancreatic adenocarcinoma. Although distinction between these two entities remains challenging, knowledge of MRI findings is important in suggesting the correct diagnosis and programming therapeutic decisions.

Treatment of advanced hepatocellular carcinoma with very low levels of amplitude-modulated electromagnetic fields.

Background:Therapeutic options for patients with advanced hepatocellular carcinoma (HCC) are limited. There is emerging evidence that the growth of cancer cells may be altered by very low levels of electromagnetic fields modulated at specific frequencies.Methods:A single-group, open-label, phase I/II study was performed to assess the safety and effectiveness of the intrabuccal administration of very low levels of electromagnetic fields amplitude modulated at HCC-specific frequencies in 41 patients with advanced HCC and limited therapeutic options. Three-daily 60-min outpatient treatments were administered until disease progression or death. Imaging studies were performed every 8 weeks. The primary efficacy end point was progression-free survival ⩾6 months. Secondary efficacy end points were progression-free survival and overall survival.Results:Treatment was well tolerated and there were no NCI grade 2, 3 or 4 toxicities. In all, 14 patients (34.1%) had stable disease for more than 6 months. Median progression-free survival was 4.4 months (95% CI 2.1–5.3) and median overall survival was 6.7 months (95% CI 3.0–10.2). There were three partial and one near complete responses.Conclusion:Treatment with intrabuccally administered amplitude-modulated electromagnetic fields is safe, well tolerated, and shows evidence of antitumour effects in patients with advanced HCC.